Tremor in Charcot-Marie-Tooth disease: No evidence of cerebellar dysfunction

•This is the first pathophysiological study of tremor in hereditary neuropathies.•This study reveals features that distinguish it from other forms of tremor, in particular the finding of a normally functioning cerebellum.•‘Neuropathic tremor’ is for the first time distinguished from other types of neuropathic tremor on the basis of mechanism, reframing this movement disorder as aetiologically heterogenous.

ObjectivesTremor in Charcot-Marie-Tooth disease (CMT) can be disabling. Cerebellar abnormalities are thought to underpin neuropathic tremor. Here, we aim to clarify the potential role of the cerebellum in CMT tremor.MethodsWe assessed prevalence of tremor by questionnaire in 84 patients with CMT. Of those, 23 patients with CMT with and without arm tremor and healthy controls underwent a clinical assessment, classical eyeblink conditioning, electro-oculography, visuomotor adaptation test, tremor recording with surface EMG and accelerometry, and retrospective correlation with nerve conduction studies to investigate the possible mechanisms of tremor generation.ResultsThe prevalence study revealed tremor in 21% of patients and in 42% of those it caused impairment of function. Tremor recordings revealed a mild-to-moderate amplitude tremor with a weight load-invariant 7.7 Hz frequency component. Performance on classical eyeblink conditioning, visuomotor adaptation and electro-oculography were no different between tremulous and non-tremulous patients and healthy controls.ConclusionsThese results argue against a prominent role for an abnormal cerebellum in tremor generation in the patients studied with CMT. Rather, our results suggest an enhancement of the central neurogenic component of physiological tremor as a possible mechanism for tremor in the patients studied.SignificanceThis study is the first to propose differing pathogenic mechanisms for subtypes of neuropathic tremor.